Endometrial HOXA-10, HOXA-11, ß-1 integrin, ECM-1, FAK, and CD44 immunohistochemical expressions in endometriosis-related recurrent IVF failure: a retrospective case-control study

Endometriosis is a common cause of infertility and is frequently associated with recurrent implantation failure in assisted reproductive technologies. Impaired endometrial receptivity, mediated by altered transcription factors, adhesion molecules, and extracellular matrix components, has been proposed as a contributing mechanism. This study aimed to evaluate compartment-specific immunohistochemical expression patterns of HOXA-10, HOXA-11, CD44, β1 integrin, ECM-1, and focal adhesion kinase (FAK) in women with endometriosis-related implantation failure. This retrospective case–control study was conducted at the IVF Unit of Gazi University Faculty of Medicine. The study group consisted of 34 infertile women with surgically confirmed endometriosis and recurrent IVF failure, subdivided into pre-receptive and receptive phases based on histological dating, while fertile women without infertility or endometriosis served as controls. Endometrial biopsies were obtained during the implantation window. Immunohistochemical expression was evaluated using semi-quantitative compartment-specific scoring, with ImageJ-based analysis used as supportive. Appropriate non-parametric statistical analyses were applied, and p < 0.05 was considered statistically significant. No statistically significant intergroup differences were observed for stromal HOXA-10 or HOXA-11 expression between control, pre-receptive, and receptive groups. Glandular CD44 positivity was significantly increased in the receptive group compared with controls, while no significant difference was detected between pre-receptive and receptive phases after multiple comparison correction. β1 integrin expression did not demonstrate consistent phase-specific differences. In contrast, strong glandular ECM-1 expression was significantly reduced in both pre-receptive and receptive groups compared with controls, whereas stromal ECM-1 expression remained unchanged. Stromal FAK expression was significantly increased in both pre-receptive and receptive groups relative to controls, with no significant difference between these phases. Endometriosis-related implantation failure is associated with distinct, compartment-specific alterations in endometrial receptivity markers that appear largely independent of physiological implantation timing. Reduced glandular ECM-1 expression and persistent stromal FAK accumulation suggest disease-specific epithelial–stromal dysregulation rather than delayed or shifted receptivity. Altered glandular CD44 expression in the receptive phase likely reflects endometriosis-associated epithelial adhesion changes rather than a phase-specific marker of functional receptivity. These findings highlight the importance of compartment-focused evaluation of endometrial receptivity in endometriosis-related infertility. This study was retrospectively conducted and was not registered in a clinical trial registry.